The Study On The Relationship Between Gestational Diabetes Mellitus And Intestinal Flora

Objective: In this study,the intestinal microflora of normal pregnant women and women with gestational diabetes mellitus was detected in early pregnancy,late pregnancy and postpartum period,and the structural characteristics of intestinal flora were analyzed combined with various clinical indexes.Through the longitudinal self-control of the changes of microflora in early pregnancy,late pregnancy and postpartum period and the horizontal control with normal pregnant women,the relationship between gestational diabetes mellitus and the structural characteristics of intestinal flora were analyzed,hoping to provide experimental basis for intervening the pathogenesis of GDM by regulating intestinal flora.Methods: 54 Pregnant women who underwent obstetrical examination in the First Affiliated Hospital of Xiamen University from March 2018 to March 2019 were divided into experimental group(GDM group,n = 27)and control group(N-GDM group,n =27),according to the results of glucose tolerance test(OGTT).The fecal samples of the two groups of pregnant women in early pregnancy,late pregnancy and postpartum period were collected,and the total DNA of the microflora was extracted from the fecal samples.The 16 s r RNA of the flora was sequenced by Hi Seq platform,bioinformatics analysis and statistical processing were carried out to analyze the characteristics and differences of microflora between the N-GDM group and the GDM group during pregnancy.Results: 1.There was no significant difference in age,pre-pregnancy weight,BMI,frequency of pregnancy and parturition,basal blood pressure and other clinical indexes between the two groups.There was no significant difference in the total weight gain during pregnancy between the two groups,but the weight gain in the late pregnancy of GDM group was significantly lower than that in the N-GDM group(P<0.001).The glycosylated hemoglobin in GDM group was significantly higher than that in N-GDM group(P<0.001).There was no statistical difference in diet,exercise and sleep between the two groups.2.The OTU of each period of the two groups gathered separately and distinguished well.The total number of OUT in GDM group was significantly higher than that in N-GDM group in late pregnancy(P <0.05).The number of independent OTU of normal pregnant women in early pregnancy and late pregnancy gradually decreased,while the number of independent OTU of pregnant women in GDM group gradually increased.3.Shannon index and simpson index in GDM group increased significantly in early pregnancy(P=0.025 、 0.018),and Beta diversity decreased significantly(P=0.002).The observed species index,ace index and chao index increased significantly in late pregnancy(P=0.045、0.041、0.034).The difference of each index in postpartum period was not statistically significance,but the Beta diversity in the postpartum group was significantly higher than that in the N-GDM group((P<0.001,P=0.004).Longitudinal observation found that,in the N-GDM group,the ace index was decreased significantly(P=0.020),while the diversity change of GDM group was not significant.4.In the N-GDM group and GDM group,the flora was mainly composed of Bacteroides and Firmicutes,followed by Proteobacteria and Actinobacteria.Among them,the proportion of Actinobacteria in early pregnancy was significantly higher than that in N-GDM group(P =0.026).In the longitudinal comparison of early pregnancy,late pregnancy and postpartum period,both GDM group and N-GDM group showed that the flora structure of early pregnancy was similar to that of postpartum period.5.There were seven species of bacteria that were significantly different between the two groups in early pregnancy,in which the characteristic flora of GDM group was Actinobacteria and the characteristic flora of N-GDM group was Spirochaetes.In the late pregnancy,there were fourteen species with significant differences,in which the characteristic flora of the GDM group was mainly Rhodobacterales and Rhodobacteraceae,while the characteristic flora of the N-GDM group was Tissierellaceae.There was no significant difference in bacterial genera between the two groups in the later stage of parturition.6.There was a significant positive correlation between Actinobacteria,Rhodobacterales,Butyricicoccus,Gemmiger and Desulfovibrio and blood glucose level,while the Spirochaetes was negatively correlated with blood glucose level.Proteobacteria,Dialister and Lachnobacterium had significant positive correlation with body weight,while Firmicutes and Veillonella had significant negative correlation with body weight.Conclusion: Compared with healthy pregnant women,the intestinal flora of pregnant women with GDM was remodeled,and the overall species diversity was higher than that of healthy pregnant women.In early pregnancy,the microflora abundance of Actinomycetes,Lactobacillus and Butylococcus in GDM pregnant women was significantly higher than that in healthy pregnant women,while in late pregnancy,the microflora abundance of Rhodobacterales and Desulfovibrio was significantly higher than that in healthy pregnant women.To sum up,GDM is closely related to the structural adjustment of intestinal flora,but the specific mechanism needs to be further studied.